Purpose :
The cause of non-infectious uveitis (NIU) is poorly understood, but is considered to be mediated by a complex interplay between multiple genetic, epigenetic and environmental factors. MicroRNAs (miRNAs) are non-coding small RNAs that control gene translation into protein. MiRNAs have been shown to be critical mediators in several pathological and inflammatory processes.

Methods :
To identify changes in circulating miRNA levels of patients with non-infectious uveitis compared with healthy controls, we exploited a high dimensional and multiple-level approach assessing and integrating the miRNA-ome and leukocyte composition in patients with NIU.Serum was collected from 54 untreated patients with active and eye-restricted disease and compared with 26 age-matched controls distributed over 2 independent cohorts. TaqMan OpenArray sequencing technology was used to screen for 753 miRNAs in serum in the first cohort. TaqMan single quantitative reverse transcription PCR (RT-qPCR) was used to validate the findings in a second, independent, cohort. Paired flow cytometry results were integrated with the miRNA data to study the relationship between miRNAs and leukocyte composition.

Results :
Using stringent selection criteria we identified and independently validated a NIU associated miRNA cluster consisting of seven microRNAs. Pathway enrichment analysis for genes targeted by these miRNAs revealed significant enrichment for the PI3K/Akt, MAPK, FOXO and VEGF signaling pathways as well as for photoreceptor development; all considered to be central pathways for various inflammatory eye conditions. In addition, high dimensional multi-level analysis of the miRNA cluster - guided by proteome and cytome data - linked the presence of the NIU-associated miRNA cluster to a different composition of leukocyte subsets, more specifically CD16+lindimCD11c+HLA-DR- cells, in these patients.